Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Capecitabine

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks

gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks

cisplatin

capecitabine

gemcitabine at 800 mg/ m2 on days 1 and 15 in arm A; at 1000 mg/m2 on days 1, 8 and 15 in arm B

gemcitabine

nab-paclitaxel at the recommended phase II dose day 1 and 15 in arm A; at 125 mg/m2 on days 1, 8 and 15 in arm B

nab-paclitaxel

Michele Reni, MD

Four-drug combo yielded a statistically significant improvement in progression-free survival and overall survival compared to gemcitabine in patients with advanced pancreatic adenocarcinoma. Nab-Paclitaxel showed promising antitumor activity in patients with pancreatic cancer. Given the synergism of taxanes with gemcitabine, fluoropyrimidines and platinating agents the role of nab-Paclitaxel in a 4-drug regimen will be explored.

The aim of this trial is to determine the recommended dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine, PAXG regimen (Phase I), and to evaluate the feasibility and the activity of the PAXG regimen in patients with stage III and IV pancreatic cancer.

OBJECTIVES: PHASE I: to determine the recommended phase 2 dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine.

PHASE II: to evaluate the feasibility and the activity of the PAXG regimen in terms of 6-months progression-free survival in patients with stage III and IV pancreatic cancer.

OUTLINE Phase I - dose finding single institution trial, followed by a randomized open label multicenter phase II trial.

Phase II: Patients will be stratified by stage (III vs IV) and CA19.9 level (\< 10 x ULN versus \>10 x ULN); Patients will be randomly assigned to receive PAXG (arm A) or gemcitabine-nab-paclitaxel regimen (arm B).

Treatment plan (phase II):

Arm A: PAXG every 4 weeks (1 cycle): cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15.

Arm B: Gemcitabine + nab-paclitaxel every 4 weeks (1 cycle): gemcitabine at 1000 mg/m2 on days 1, 8 and 15; nab-paclitaxel at 125 mg/mq on days 1, 8 and 15.

Treatment will be administered for a maximum of 6 cycles or until there is a clinical benefit.

A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma

Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs:

* Hematologic toxicity

  * Grade ≥ 4 neutropenia lasting 7 days or more
  * Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C
  * Grade 4 thrombocytopenia
  * Grade 3 thrombocytopenia which required transfusions
* Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy
* Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event
* Neurological toxicity Any Grade ≥ 2 neurological toxicity
* Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline)
* Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by \> 2 weeks.

rate of progression-free patients at 6 months from randomization

rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start

contrast enhanced CT scan tumor assessment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma	NCT01730222	Pancreatic Canc...	cisplatin capecitabine gemcitabine nab-paclitaxel	18 Years - 75 Years	IRCCS San Raffaele
A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma	NCT01730222	Pancreatic Canc...	cisplatin capecitabine gemcitabine nab-paclitaxel	18 Years - 75 Years	IRCCS San Raffaele
A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma	NCT01730222	Pancreatic Canc...	cisplatin capecitabine gemcitabine nab-paclitaxel	18 Years - 75 Years	IRCCS San Raffaele

Spots Global Cancer Trial Database for stage iii disease